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4js0

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{{STRUCTURE_4js0| PDB=4js0 | SCENE= }}
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==Complex of Cdc42 with the CRIB-PR domain of IRSp53==
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===Complex of Cdc42 with the CRIB-PR domain of IRSp53===
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<StructureSection load='4js0' size='340' side='right' caption='[[4js0]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24584464}}
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== Structural highlights ==
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[[4js0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JS0 OCA]. <br>
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<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
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== Publication Abstract from PubMed ==
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The Rho family GTPase effector IRSp53 has essential roles in filopodia formation and neuronal development, but its regulatory mechanism is poorly understood. IRSp53 contains a membrane-binding BAR domain followed by an unconventional CRIB motif that overlaps with a proline-rich region (CRIB-PR) and an SH3 domain that recruits actin cytoskeleton effectors. Using a fluorescence reporter assay, we show that human IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB-PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain. The crystal structure of Cdc42 bound to the CRIB-PR reveals a new mode of effector binding to Rho family GTPases. Structure-inspired mutations disrupt autoinhibition and Cdc42 binding in vitro and decouple Cdc42- and IRSp53-dependent filopodia formation in cells. The data support a combinatorial mechanism of IRSp53 activation.
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==Function==
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Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors.,Kast DJ, Yang C, Disanza A, Boczkowska M, Madasu Y, Scita G, Svitkina T, Dominguez R Nat Struct Mol Biol. 2014 Mar 2. doi: 10.1038/nsmb.2781. PMID:24584464<ref>PMID:24584464</ref>
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[[http://www.uniprot.org/uniprot/CDC42_HUMAN CDC42_HUMAN]] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.<ref>PMID:14978216</ref> <ref>PMID:15642749</ref> <ref>PMID:17038317</ref> [[http://www.uniprot.org/uniprot/BAIP2_HUMAN BAIP2_HUMAN]] Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection.<ref>PMID:11130076</ref> <ref>PMID:11696321</ref> <ref>PMID:14752106</ref> <ref>PMID:19366662</ref>
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==About this Structure==
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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[[4js0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JS0 OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:024584464</ref><references group="xtra"/><references/>
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</StructureSection>
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[[Category: Human]]
[[Category: Dominguez, R.]]
[[Category: Dominguez, R.]]
[[Category: Kast, D J.]]
[[Category: Kast, D J.]]

Revision as of 05:31, 30 April 2014

Complex of Cdc42 with the CRIB-PR domain of IRSp53

4js0, resolution 1.90Å

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